Author Archives: David Worrell

Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice.

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Pharmacology Biochemistry and Behavior“Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders.

Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine.

In summary, the outcomes of the present study showed that activation and inhibition of CB1 receptors as well as inhibition of CB2 receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB1 and CB2 receptors has a potential to augment the antidepressant activity of agomelatine.”

https://www.ncbi.nlm.nih.gov/pubmed/31785246

https://www.sciencedirect.com/science/article/pii/S0091305719304873?via%3Dihub

Cannabis for pain in orthopedics: a systematic review focusing on study methodology

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Image result for Can J Surg. journal“Medical cannabis use is an emerging topic of interest in orthopedics. Although there is a large amount of literature on medical cannabis use for managing various types of pain, few studies have focused on orthopedic conditions. There is little high-quality evidence in core orthopedic areas. The objective of this study was to summarize the literature on the efficacy of cannabis use for pain related to orthopedic conditions.

METHODS:

We conducted a systematic review of the literature on the use of cannabinoids for pain management in core orthopedic conditions. Two independent reviewers extracted information on reporting quality, risk of bias, drugs, population, control, duration of study, pain outcomes and the authors’ conclusions regarding efficacy for pain outcomes.

RESULTS:

We identified 33 orthopedic studies, including 21 primary studies and 12 reviews. Study quality was generally low to moderate. Six of the included studies had a control group and 15 were noncontrolled studies. Methodologies, drugs and protocols of administration varied greatly across studies. Study conclusions were generally positive in noncontrolled studies and mixed in controlled studies. Studies using higher doses tended to conclude that cannabis use was effective, but the potential for harmful effects may also be increased with higher doses.

CONCLUSION:

Variability in the methodologies used in cannabis research makes it challenging to draw conclusions about dosing, routes and frequency of administration. Most of the existing evidence suggests that medical cannabis use is effective, but this efficacy has been demonstrated only when either there is no comparator or cannabis is compared with placebo. Studies using an active comparator have not demonstrated efficacy. Future research should focus on improving study reporting and methodologic quality so that protocols that optimize pain control while minimizing harmful effects can be determined.”

https://www.ncbi.nlm.nih.gov/pubmed/31782292

The use of medical grade cannabis in Italy for drug-resistant epilepsy: a case series.

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 “In Italy, medical grade cannabis (MGC) can be prescribed for different medical conditions, including drug-resistant epilepsy (DRE), once standard and approved therapies have failed, or caused non-tolerable side effects.

Here, we present a retrospective case series report of five patients with DRE who started therapy with MGC. Authorized ISO 9001:2008 pharmacies prepared MGC according to Italian laws. Olive oil extracts (OOEs) were prepared following standard extraction protocols, and cannabinoids were measured on each OOE to check for successful extraction.

After treatment with MGC, all patients reported a reduction in seizure frequency and severity, and some reported improved mood, sleep quality, and general well-being without relevant side effects.

Despite the small sample size and open-label nature of the data, we show that MGC may be successfully used to treat DRE. This is especially true when considering that no valid therapeutic option exists for these patients and that MGC was extremely well tolerated.”

https://www.ncbi.nlm.nih.gov/pubmed/31776867

https://link.springer.com/article/10.1007%2Fs10072-019-04162-1

Exploring cancer survivors’ attitudes, perceptions, and concerns about using medical cannabis for symptom and side effect management: A qualitative focus group study.

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Complementary Therapies in Medicine“The purpose of this study is to gain a greater understanding of cancer survivors’ attitudes, perspectives, and concerns about medical cannabinoids (MCs) for cancer symptom and side effect management.

Using qualitative methods, we conducted four focus groups (n = 19) with cancer survivors recruited from a community-based cancer wellness center. Groups were audio-recorded and facilitated by experienced co-moderators who directed discussion using a semi-structured interview guide. Transcripts were coded using principles from Grounded Theory.

Analyses revealed the following ten themes and percentages of codes applied: 1) Attitudes & Beliefs (25.3%), 2) Access (17.1%), 3) Information (15.5%), 4) Concern (14%), 5) How MCs Helped (12.6%), 6) Comfort (4.3%), 7) Confusion (3.6%), 8) Trust/Distrust (3.1%), 9) Behaviors (2.3%), and 10) Support (2.2%).

Participants reported that MCs offer potential benefits for symptom management and side effect relief, especially in reducing and managing pain. Despite the growing number of states that are legalizing MCs, significant barriers exist that make knowledge and adequate access a challenge for many.”

https://www.ncbi.nlm.nih.gov/pubmed/31779995

https://www.sciencedirect.com/science/article/abs/pii/S0965229919309252?via%3Dihub

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

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 ijms-logo“Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.”

https://www.ncbi.nlm.nih.gov/pubmed/31775230

https://www.mdpi.com/1422-0067/20/23/5905

Monocyclic Quinone Structure-Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Antiproliferative Activity.

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Publication cover image“The monocyclic 1,4-benzoquinone, HU-331, the direct oxidation product of cannabidiol, inhibits the catalytic activity of topoisomerase II but without inducing DNA strand breaks or generating free radicals, and unlike many fused-ring quinones exhibits minimal cardiotoxicity. Thus, monocyclic quinones have potential as anticancer agents, and investigation of the structural origins of their biological activity is warranted. New syntheses of cannabidiol and (±)-HU-331 are here reported. Integrated synthetic protocols afforded a wide range of polysubstituted resorcinol derivatives; many of the corresponding novel 2-hydroxy-1,4-benzoquinone derivatives are potent inhibitors of the catalytic activity of topoisomerase II, some more so than HU-331, whose monoterpene unit replaced by a 3-cycloalkyl unit conferred increased antiproliferative properties in cell lines with IC50 values extending below 1 mM, and greater stability in solution than HU-331. The principal pharmacophore of quinones related to HU-331 was identified. Selected monocyclic quinones show potential for the development of new anticancer agents.”

https://www.ncbi.nlm.nih.gov/pubmed/31778038

https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201900548

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases.

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 ijms-logo“Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target.”

https://www.ncbi.nlm.nih.gov/pubmed/31771129

https://www.mdpi.com/1422-0067/20/23/5875

The curative effect of a cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion.

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Publication cover image“As we learn more about the endocannabinoid system (ECS), our understanding and grasp of the system’s ubiquitous presence is expanding. In light of this, there is also a growing body of evidence for the therapeutic potential of ECS modulation in a range of clinical situations. Strategies include for example manipulation of the Cannabinoid 1 (CB1) receptor, mostly in terms of CNS processes, and activation of the Cannabinoid 2 (CB2) receptor as anti-inflammatory target.”

https://www.ncbi.nlm.nih.gov/pubmed/31774568

https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12524

Cannabinoids for drug-resistant seizures in a critically ill patient-Case report and literature review.

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Publication cover image“Drug-resistant seizures are life-threatening and contribute to sustained hospitalization.

We present the case of a critically ill 28-year-old male with Lennox-Gastaut syndrome who had approximately 30 seizures/day in the intensive care unit.

CASE DESCRIPTION:

Patient required mechanical ventilation and pharmacologically induced thiopentone coma.

He was commenced on cannabidiol and subsequently extubated.

He remained seizure-free thereafter on a combination of cannabidiol and anti-epileptic medication that predated his critical illness.

WHAT IS NEW AND CONCLUSION:

Our case report provides a unique perspective on the role of cannabidiol in achieving remission from drug-resistant seizures in critically ill patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31770462

https://onlinelibrary.wiley.com/doi/abs/10.1111/jcpt.13082

Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling.

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 JACC: Basic to Translational Science“Excessive binge alcohol drinking may adversely affect cardiovascular function. In this study we characterize the detailed hemodynamic effects of an acute alcohol binge in mice using multiple approaches and investigate the role of the endocannabinoid-cannabinoid 1 receptor (CB1-R) signaling in these effects. Acute alcohol binge was associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction lasting for several hours and redistribution of circulation. These changes were attenuated by CB1-R antagonist or in CB1-R knockout mice. Our results suggest that a single alcohol binge has profound effects on the cardiovascular system, which involve endocannabinoid-CB1-R signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31768478

“Alcohol is one of the most frequently used intoxicants in the United States. Binge alcohol drinking is a major contributor of emergency department visits. Binge alcohol drinking may adversely affect cardiovascular function. Here we show that acute alcohol intoxication is associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction and blood redistribution lasting for several hours. The adverse cardiovascular effects of acute alcohol intoxication are attenuated by CB1-R antagonist or in CB1-R knockout mice. A single alcohol binge has profound effect on the cardiovascular system, which involves endocannabinoid-CB1-R signaling.”

https://www.sciencedirect.com/science/article/pii/S2452302X19301755?via%3Dihub